Vaccines against Streptococcus pyogenes (the Lancefield group A streptococcus; GAS) have long been sought due to the debilitating diseases caused by the bacterium, particularly rheumatic fever and rheumatic heart disease. Rheumatic fever is an uncommon disease today in most developed countries but it remains the major cause of acquired heart disease in children, adolescents and young adults in the developing world. In addition, invasive GAS disease is a frequent cause of sepsis in children and adults and has a high-case fatality rate. Further adding to the burden of GAS disease is post-streptococcal glomerulonephritis, which likely contributes to the high rates of end-stage renal failure in many GAS endemic regions. GAS pharyngitis and impetigo are responsible for the greatest absolute number of GAS infections each year. GAS pharyngitis affects approximately 8%-15% of school-aged children per year and GAS impetigo is a very common infection in children prevalence of 10-50%. Not only are severe GAS-associated diseases a problem in developing countries, but even in developed countries particularly virulent GAS strains have emerged that are resistant to standard antibiotic therapies and cause debilitating diseases such as severe necrotizing fasciitis.
An important virulence factor of GAS is M protein, which is strongly anti-phagocytic and binds to serum factor H, destroying C3-convertase and preventing opsonization by C3b. Vaccines have been developed that contain immunogenic peptides from the conserved C-repeat portion of the M protein, such as T and B-cell epitopes from the C-repeat region or the J8 and J14 peptide vaccines that contain single, minimal B cell epitopes from this C-repeat region.